Continuous phase compositions for ACL repair

ABSTRACT

An implantable interference screw for use in a soft tissue repair, the screw having a bioresorbable body comprising a plurality of interconnected pores, the body having an instrument interface in one end and a thread around an exterior of the body starting from distal end. The plurality of interconnected pores of the resorbable body are substantially filled with a bioresorbable polymer.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation-in-part of U.S. patent applicationNo. 11/008,075, filed on Dec. 9, 2004, now U.S. Pat. No. 7,879,109,issued on Feb. 1, 2011. The disclosure of the above application isincorporated herein by reference.

INTRODUCTION

The statements in this section merely provide background informationrelated to the present disclosure and may not constitute prior art.

In general, the human musculoskeletal system is composed of a variety oftissues including bone, ligaments, cartilage, muscle, and tendons.Tissue damage or deformity stemming from trauma, pathologicaldegeneration, or congenital conditions often necessitates surgicalintervention to restore function. During these procedures, surgeons canuse orthopedic implants to restore function to the site and facilitatethe natural healing process.

When a ligament becomes detached from a bone, surgery usually isrequired to reconstruct the ligament. The reconstruction of ligaments,including anterior cruciate ligaments (ACL) and posterior cruciateligaments (PCL) using autologous ligament grafts, allografts, orartificial grafts, is well known. The ACL and PCL procedures may beperformed arthroscopically and, generally, involve preparing a bonetunnel through the tibia and adjacent femur, placing a ligament graftextending between the two bone tunnels, and securing each end of thegraft within its respective tunnel. Various methods of graft attachmentare known, including the use of interference screws to secure the graftagainst the wall of the graft tunnel. A metal interference screw may beused to wedge a graft bone block to the wall of the graft tunnel. If abioabsorbable interference screw is used, the graft may be wedgeddirectly against the bone by the interference screw, without a boneblock.

Interference screws are generally composed of non-resorbable metals,ceramics, polymers, and composites. Interference screws for anchoringligaments to bone are typically fabricated from medically approvedmetallic materials that are not naturally absorbed by the body. Adisadvantage of such interference screws is that once healing iscomplete, an additional surgical procedure may be required to remove theinterference screw from the patient. Metallic interference screws mayinclude a threaded shank joined to an enlarged head having a transverseslot or hexagonal socket formed therein to engage a similarlyconfigured, single blade or hexagonal rotatable driver for turning theinterference screw into the bone. The enlarged heads on suchinterference screws can protrude from the graft tunnel and can causechronic irritation and inflammation of surrounding body tissue.

Permanent metallic interference screws in movable joints can, in certaininstances, cause abrading of ligaments during normal motion of thejoint. Interference screws occasionally back out after insertion,protruding into surrounding tissue and causing discomfort. Furthermore,permanent metallic interference screws and fixation devices may shieldthe bone from beneficial stresses after healing. It has been shown thatmoderate periodic stress on bone tissue, such as the stress produced byexercise, helps to prevent decalcification of the bone. Under someconditions, the stress shielding which results from the long term use ofmetal bone fixation devices can lead to osteoporosis.

However, in some instances, it may be desirable to have an interferencescrew made of resorbable material. These bioabsorbable, resorbable, orbiodegradable materials are characterized by the ability to bechemically broken down into harmless by-products that are metabolized orexcreted by the body. Materials of this type can offer an advantage overconventional non-resorbable implant materials. A bioabsorbableinterference screw provides the required function until the tissue ishealed, and once the role of the screw is complete, it is resorbed bythe body. The end result is healthy tissue with no signs that an implantwas ever present.

Biodegradable or bioabsorbable interference screws have been proposed toavoid the necessity of surgical removal after healing. Because thedegradation of a biodegradable screw occurs over a period of time, thesupport load is transferred gradually to the bone as it heals reducingpotential stress shielding effects. Conventional bioabsorbableinterference screws are softer and weaker than metallic compositionssuch that they are not self-tapping, thereby requiring the holes drilledinto the bone to be tapped. The necessity to tap holes in the injuredbone adds to the complexity of the surgical procedure and lengthens thetime required to complete the operation.

Considerable effort has been expended to increase the stiffness andstrength of bioabsorbable materials through various compositetechnologies, such as incorporating strong, stiff, non-absorbable,inorganic structural fibers or particles made from carbon or glass, asreinforcing agents in a bioabsorbable polymeric matrix. The disadvantageof this approach is that the non-absorbable fibers remain in the bodytissue after the bioabsorbable polymer has been absorbed and may migrateor cause tissue inflammation. Composite bioabsorbable screws may also beprepared by incorporating inorganic, bioabsorbable glass or ceramicreinforcement fibers or particles in a bioabsorbable polymeric matrix.However, lack of reinforcement-to-matrix interfacial bonding leads topoor load transfer between the reinforcement and the matrix. Theweakness of the interface is accentuated when the implants are placed inthe human body and may result in compromised long-term performance.

Reinforced bioabsorbable composite screws have also been made by addingan organic bioabsorbable reinforcing fiber to a bioabsorbable polymermatrix. Similarly, highly drawn fibers of PLA or PGA can be fused toform a bioabsorbable polymeric screw with increased stiffness andstrength. Unfortunately, the consolidation or the melting temperature ofthe matrix usually causes the organic biocompatible reinforcing fibersto partially relax their molecular orientation, thereby losing theirstrength and stiffness and adversely affecting the properties of thecomposite. Until now, the efforts to utilize bioabsorbable materials fororthopedic load-bearing applications have not been entirely successful.

SUMMARY

Various embodiments of the present technology provide an implantablebioabsorbable interference screw, also referred to herein as an implant,for use in soft tissue repair. The interference screw comprises abioabsorbable body, which has a plurality of interconnecting pores. Theplurality of interconnecting pores in the bioabsorbable body issubstantially filled with a bioresorbable polymer. In variousembodiments, the interference screw has an instrument interface on oneend and a thread starting at a tapered distal end. Methods of use of theimplantable bioabsorbable interference screw and kits that include atleast one bioabsorbable interference screw are also provided.

It has been found that compositions, devices, and methods of the presenttechnology provide advantages over compositions, devices, and methodsamong those in the art. Such advantages may include one or more of easeof surgical implementation, increased strength of ligament repair,reduced healing time, and decreased surgical side effects.

Further areas of applicability will become apparent from the descriptionprovided herein. It should be understood that the description andspecific examples are intended for purposes of illustration only and arenot intended to limit the scope of the present disclosure.

DRAWINGS

The drawings described herein are for illustration purposes only and arenot intended to limit the scope of the present disclosure in any way.

FIG. 1 is a perspective detailed view of a scaffold according to variousembodiments;

FIG. 2 is a perspective detailed view of a continuous phase compositeaccording to various embodiments;

FIG. 3 is a graph comparing compressive strength over time of acontinuous phase composite and a pure polymer sample according tovarious embodiments;

FIG. 4 is an implant according to various embodiments;

FIG. 5 is an implant according to various embodiments;

FIG. 6 is an implant according to various embodiments;

FIG. 7 is an implant according to various embodiments;

FIG. 8 is an implant according to various embodiments;

FIG. 9 is an implant according to various embodiments;

FIG. 10 is an implant according to various embodiments;

FIG. 11 illustrates a method of forming an implant according to variousembodiments;

FIG. 12 is a flow chart illustrating a method of selecting material forthe forming of an implant according to various embodiments;

FIG. 13 is a cross-sectional view of an example of attaching an ACL inthe tibia employing an implant according to various embodiments; and

FIG. 14 is a cross-sectional view of an example of a surgicallyreconstructed ACL employing an implant according to various embodiments.

It should be noted that the drawings set forth herein are intended toexemplify the general characteristics of devices, materials, and methodsamong those of this technology, for the purpose of the description ofsuch embodiments herein. These drawings may not precisely reflect thecharacteristics of any given embodiment, and are not necessarilyintended to define or limit specific embodiments within the scope ofthis technology.

DESCRIPTION

The following description of technology is merely exemplary in nature ofthe subject matter, manufacture and use of one or more inventions, andis not intended to limit the scope, application, or uses of any specificinvention claimed in this application or in such other applications asmay be filed claiming priority to this application, or patents issuingtherefrom. The following definitions and non-limiting guidelines must beconsidered in reviewing the description of the technology set forthherein.

The headings (such as “Introduction” and “Summary”) used herein areintended only for general organization of topics within the disclosureof the teachings, and are not intended to limit the disclosure of theteachings or any aspect thereof. In particular, subject matter disclosedin the “Introduction” may include aspects within the scope of the noveltechnology and may not constitute a recitation of prior art. Subjectmatter disclosed in the “Summary” is not an exhaustive or completedisclosure of the entire scope of this technology or any embodimentsthereof. Classification or discussion of a material within a section ofthis specification as having a particular utility (e.g., as being a“bone ingrowth promoting agent” component) is made for convenience, andno inference should be drawn that the material must necessarily orsolely function in accordance with its classification herein when it isused in any embodiments of the present technology.

The citation of references herein and during prosecution of thisapplication does not constitute an admission that those references areprior art or have any relevance to the patentability of the technologydisclosed herein. Any discussion of the content of references cited isintended merely to provide a general summary of assertions made by theauthors of the references, and does not constitute an admission as tothe accuracy of the content of such references. All references cited inthe “Description” section of this specification are hereby incorporatedby reference in their entirety.

The description and specific examples, while indicating embodiments ofthe technology, are intended for purposes of illustration only and arenot intended to limit the scope of the technology. Moreover, recitationof multiple embodiments having stated features is not intended toexclude other embodiments having additional features, or otherembodiments incorporating different combinations of the stated features.Specific examples are provided for purposes of illustration only of howto make and use the devices and methods of this technology and, unlessexplicitly stated otherwise, are not intended to be a representationthat given embodiments have, or have not, been made or tested.

As used herein, the word “include” and its variants is intended to benon-limiting, such that recitation of items in a list is not to theexclusion of other like items that may also be useful in the materials,compositions, devices, and methods of these teachings. The terms “a” and“an” mean at least one. Also, all compositional percentages are byweight of the total composition, unless otherwise specified.

The present technology provides medical implants, in particularincluding implantable screws, comprising a bioabsorbable structurematerial having a plurality of interconnecting pores and bioresorbablepolymer filling at least a portion of said plurality of interconnectingpores. For ease of discussion, FIGS. 4-10 and 13-14 depictrepresentative medical implants. It is understood, however, that thepresent technology encompasses a wide variety of implants, used for awide variety of therapeutic and cosmetic applications, in human or otheranimal subjects. The specific devices and materials used must,accordingly, be biomedically acceptable. As used herein, such a“biomedically acceptable” component is one that is suitable for use withhumans or other animals without undue adverse side effects (such astoxicity, irritation, and allergic response) commensurate with areasonable benefit/risk ratio.

Screw Body Composition

With reference to FIG. 1, a structure 10 for an implantable screw bodystructure is illustrated. In various embodiments, the structure 10 maybe formed of natural sources of biocompatible, bioresorbable and/orbioabsorbable materials, such as coral. In various embodiments,synthetic materials may be used to form the structure 10. Thesematerials may include absorbable ceramics, absorbable polymers, or anyother absorbable porous matrix. In various embodiments, the porousmaterial may include the bioresorbable ceramic sold under the trade namePro Osteon 500R™ by Interpore Spine Ltd. (Irvine, Calif., USA), ProOsteon 200R™ by Interpore Spine Ltd. (Irvine, Calif., USA), CalcigenPSI™ by Biomet (Warsaw, Ind., USA), or OsteoStim™ by EBI (Parsippanny,N.J., USA). Porous materials useful herein include those disclosed inU.S. Pat. No. 4,976,736, White et al., issued Dec. 11, 1990; and U.S.Pat. No. 6,376,573 White et al, issued Apr. 23, 2002, which are herebyincorporated by reference.

The Pro Osteon material consists of an interconnected or continuousporous calcium carbonate substrate with a thin surface layer ofhydroxyapatite. Various other exemplary porous materials may includecalcium carbonate, tricalcium phosphate, biphasic calcium phosphate, orany appropriate calcium based ceramic. It will also be understood thatthe structure 10 may be any appropriate combination of materials, suchas including one material as a coating on another.

In various embodiments, the structure 10 may be formed from a polymer. Apolymer matrix may define a porous structure similar to the structure10. The material of the polymer matrix may be any appropriate polymersuch as a biocompatible, bioresorbable and/or bioabsorbable polymer,including those discussed herein. Thus, it will be understood that thestructure 10 may be formed of any appropriate material, including aresorbable ceramic, a polymer, a composite, and combinations thereof,etc.

The structure 10 itself may be used for various purposes, such as a boneregeneration scaffold or bone graft replacement. Nevertheless, thephysical properties of the structure 10 can be augmented for variousreasons. For example, the structure 10 alone may not include a selectedphysical property, such as a selected compressive strength, tensilestrength, torsion strength, or the like. Thus, the structure 10 may beaugmented to improve its properties allowing for greater use as asurgical device, as discussed herein in various embodiments.

To augment the structure 10, a second material 21 may be added thereto,such as during formation of the structure 10 itself or at a later time.For example, the second material 21 may be injected into or otherwiseprovided into a plurality of pores 16 defined by the structure 10. Thestructure 10 can include a channel or plurality of pores 16 that may besubstantially continuous or interconnected pores 16. The pores 16 maydefine a plurality of sizes of pores or porous structures. For example,the pores 16 may range from about 0.1 nanometers (nm) to about 1 mm.

It will be understood that the pores 16 may be any opening that allowsaccess to the interior of the structure 10. For example, there may beinterstitial spaces defined between the portions that defined thechannels interconnecting other pores 16. In various embodiments, thepores 16 define a generally interconnected path throughout the structure10. The pores 16 may be connected with other pores 16 or channels toform the interconnected or continuous pores 16 or channels. Also thevarious channels may be interconnected such that more than a singlechannel or two openings may be interconnected in the structure 10. Theinterconnected nature of the pores 16 may be referred to as a continuousphase throughout the structure 10. The continuous phase may also beunderstood to be interconnected pores 16 that are defined by a solidportion of the structure 10. Moreover, in various embodiments, the pores16 generally extend through the structure 10 such that a path can betraced from a first side 10 a of the structure 10 to a second side 10 bof the structure, or from an entrance path to an exit path that canenter and exit from any sides, or from the same side.

The different sized pores 16 or channels may be used with or arespecifically applicable to different types of surgical indications. Forexample, with reference to FIG. 2, the pores 16, such as those generallyranging from about 10 nm to about 1 mm, may be filled with the secondmaterial 21, which may be, for example, a selected polymer.Macroporosity, as used herein, relates to the structure 10 comprisingpores 16 with diameters about 100 μm or greater. Mesoporosity, as usedherein, relates to structure 10 comprising pores 16 with diameters thatrange from about 10 μm to about 100 μm. Microporosity, as used herein,relates to the structure 10 comprising pores 16 with diameters fromabout 10 μm to less than 0.01 μm. In various embodiments, structure 10may comprise pores 16 that have macroporosity, mesoporosity,microporosity, or combinations thereof. In various embodiments,structure 10 may comprise pores 16 having a diameter of about 190microns to about 230 microns, and an exemplary structure 10 usefulherein may be Pro Osteon 200R™ by Interpore Spine Ltd. (Irvine, Calif.,USA). In various embodiments, structure 10 may comprise pores 16 withdiameters of about 350 microns to about 600 microns and an exemplarystructure 10 may be Pro Osteon 500R™ by Interpore Spine Ltd. (Irvine,Calif., USA). In various embodiments, the surface of pores 16 maycomprise a coating 14, and examples of coating 14 useful herein mayinclude calcium sulfate, calcium carbonate, and/or calcium phosphate.The second material 21 may be injection molded in a semi-liquid, moltenform to fill the macroporosity defined by the structure 10, such as thepore 16 sizes that are operable or easily filled with the polymer in aflowable state. Various polymers may be used as the second material 21to fill a selected porosity of the structure 10. For example,bioabsorbable, bioabsorbable, biocompatible materials, or anyappropriate combination of materials may be used.

Suitable absorbable materials useful for structure 10 may include, butare not limited to, glasses or ceramics comprising mono-, di-, tri-,α-tri-, β-tri-, and tetra-calcium phosphate, hydroxyapatite, calciumsulfates, calcium oxides, calcium carbonates, magnesium calciumphosphates, phosphate glass, bioglass, mixtures thereof or a stiff,strong polymer, such as a PLA polymer.

In various embodiments, the second material 21 may include PLA. Forexample, PLA may be provided that includes a compositional ratio ofabout 70:30 poly(L/D,L lactic acid). The specific ratio of variouschiral monomers in the polymer is merely exemplary and any appropriateratio may be used. Nevertheless, herein the 70:30 poly(L/D,L lacticacid) may be referred to as PLDLLA. Other polymers may include acopolymer of lactic acid and glycolic acid. It will be understood,however, that any appropriate polymer material may be used as the secondmaterial 21 to form the composite 20. Other bioresorbable, biocompatiblepolymers include poly(glycolic acid), poly(carbonate), poly(urethane),poly(amino acids), poly(phosphazenes), poly(hydroxyacids),poly(anhydrides), poly(dioxanone), poly(hydroxybutyrate), andpoly(caprolactone). Also, copolymers of these or other appropriatemonomers may be used. Further, as discussed above, the structure 10 maybe formed of a polymer matrix including these polymers or copolymers.The selected polymer that may be used with the structure 10, however,may be injection molded or otherwise fill the pores 16 defined by thestructure 10. The second material 21 may fill the pores 16 of thestructure 10 to form a substantially solid structure. Nevertheless, thecomposite 20 may still include a selected porosity or open pores 16 orchannels even when filled with the second material 21. Also, it may beselected to fill the pores 16 less than completely, therefore, leavingan open space in at least a portion of the pores 16 even if they mayinclude some of the second material 21. For example, pores 16 having asize of about 0.01 μm to about 10 μm may still remain in the composite20 after the second material 21 is injected for the second material 21fills the larger pores 16 or macro pores of the structure 10. The pores16 that are generally less than about 10 μm, may be referred to hereinas micropores or microporosity. The microporosity, however, is notnecessary and may not always be present. For example, with variouspolymer filling techniques, such as polymerization of a positionedmonomer discussed herein, the microporosity may be substantially less ornon-existent in the composite 20. As is generally understood, a polymeris generally formed of a single monomer while a copolymer generallyincludes at least two types of monomers.

In various embodiments, suitable materials useful for the secondmaterial. 21 include biocompatible polymers selected from the groupconsisting of aliphatic polyesters, polyorthoesters, polyanhydrides,polycarbonates, polyurethanes, polyamides, polyalkylene oxides, andcombinations thereof. In various embodiments, the second material 21 maybe formed from aliphatic polymers, polyesters, copolymer polyesters andblends thereof. The aliphatic polyesters are typically synthesized in aring opening polymerization. Suitable monomers include, but are notlimited to, lactic acid, lactide (including L-, D-, meso and D,Lmixtures), glycolic acid, glycolide, ε-carprolactone, p-dioxanone(1,4-dioxan-2-one), trimethylene carbonate (1,3-dioxan-2-one),δ-valerolactone, β-butyrolactone, ε-decalactone, 2,5-diketomorpholine,pivalolactone, α,α-diethylpropiolactone, ethylene carbonate, ethyleneoxalate, 3-methyl-1,4-dioxane-2,5-dione,3,3-diethyl-1,4-dioxan-2,5-dione, gamma-butyrolactone,1,4-dioxepan-2-one, 1,5-dioxepan-2-one, 6,6-dimethyl-dioxepan-2-one,6,8-dioxabicycloctane-7-one, and combinations thereof. These monomersgenerally are polymerized in the presence of an organometallic catalystand an initiator at elevated temperatures.

In various embodiments, the composition of the implantable screw isselected to optimize one or more selected properties, such as acompressive strength after a selected time period after implantation, orthe amount of time generally necessary for bone ingrowth to form aselected fusion. Therefore, a polymer may be chosen for the secondmaterial 21 of the composite 20. For example, the PLDLLA second material21, discussed above, may form about 60% of the composite 20 with about40% of the composite 20 being the structure 10 formed of the Pro Osteon500R ™. Such a combination can achieve a compressive strength of about1500 N to about 3000 N at about 6 months after implantation. In variousembodiments, other second materials 21 and other structures 10 may beused to achieve similar results or varying results to meet the needs ofthe composite 20.

In various embodiments, a fast resorption of the composite 20 may beselected. For example, in a fracture, healing or repair may be fasterthan in a fusion. Therefore, an interference screw that is substantiallyresorbed after about 3 months to about 6 months may be selected. Such animplant may be formed with a copolymer of lactic acid and glycolic acid.The copolymer can be about 85% lactic acid and about 15% glycolic acid,similar to the material sold as Lacotsorb™ by Biomet, Inc. Animplantable screw or implant, including such a copolymer, can be about60% of the composite 20 while the other about 40% is formed of the ProOsteon may be used in a fracture situation. For example, an implantablescrew or implant (70, 90, 110, 130, 170, 200, 220) may be formed of sucha composition for use as an interference screw in an ACL replacementprocedure to provide a selected time when the graft is no longer heldwith the implant (70, 90, 110, 130, 170, 200, 220).

Also, the second material 21 may be a polymer, or a slower resorbingmaterial and, as such, may be selected based upon inherent properties orones formed therein. For example, a slower resorbing second material 21may generally be a polymer having a higher molecular weight. Thus, theslower the implant should resorb or the longer a selected property, suchas compressive strength is needed, the higher the molecular weight ofthe polymer that may be chosen for the second material 21. However, itwill also be understood that selected second materials 21 may includeproperties that may be achieved by a polymer having a lower molecularweight. Also, selected strengths of the second material 21 may beinherent in a polymer itself, rather than a selected molecular weightthereof.

In various embodiments, the composite 20 can include a dual ceramic. Thestructure 10 can be formed of a first ceramic including a first propertyand the pores 16 or channels may be filled with a second ceramic (secondmaterial 21), rather than a polymer, and the second ceramic having asecond property. The different properties can include resorption rates,compressive strengths, torsion strengths, or the like. This can beachieved by casting a ceramic slurry into the porosity of the structure10. The slurry can undergo a chemical reaction to set into a hardenedform or it can be sintered to form a rigid ceramic phase.

Also, two polymers that independently may have different properties canbe used to form the composite 20. For example, a first polymer, having afirst property, may be used to form the structure 10 that includes aselected porosity and/or channels. The porosity of the structure 10 canbe filled with the second material 21 (a second polymer) having a secondproperty. Again, the properties of the two polymers may include acompressive strength, a resorption rate, a tensile strength, or thelike. This can be achieved through injection molding, in situpolymerization, and solution-casting techniques, as described herein.

It will be understood that the composite 20 may be a substantially dualphase or greater composite 20 so that it will react in a substantiallyuniform manner when implanted in the body. The phases can refer to thephase of the structure 10 and the phase of the second material 21positioned in the pores 16 or channels of the structure 10, such as abioresorbable polymer. According to various embodiments, the composite20 may be about 30 weight percent (wt %) to about 70 wt % the secondmaterial 21 (a polymer fill) and about 30 wt % to about 70 wt %structure 10. For example, the composite 20 may be about 55 wt % toabout 65 wt % the second material 21 (a polymer fill) and about 45 wt %to about 55 wt % ceramic structure 10. Nevertheless, the composite 20may be substantially 100 wt % polymer if the structure 10 is formed froma porous polymer matrix. In this case, the composite 20 may be about 30wt % to about 70 wt % the second material 21 (a polymer fill) and about30 wt % to about 70 wt % structure 10, a porous polymer matrix. The sameapplies to a substantially 100% ceramic composite 20 having both a slowand fast resorbing ceramic.

Both phases, that being the structure 10 phase and the second material21 phase, may be substantially continuous. This means, according tovarious embodiments, that the second material 21 phase is substantiallyinterconnected throughout the composite 20 and that structure 10 phaseis also substantially interconnected. Such results can be obtained byusing an intact structure 10 phase rather than a particle. It will beunderstood that an appropriate structure 10 phase may be formed fromparticles. By filling the porosity of the structure 10 phase with thesecond material 21, the resulting composite 20 is effectively composedof two or more distinct, intact, and continuous phases. As discussedherein, the different resorption rates of the continuous phases (forexample, structure 10 and the second material 21) within the composite20 results in a resorption profile that can include a slowly degradingphase and a quickly degrading phase. The quickly degrading phase canallow for tissue ingrowth as the phase is resorbed whereas the slowlydegrading phase provides the implant site with mechanical support. Itwill be understood that either the structure 10 or the second material21 may be formed to be the quicker resorbing phase.

The composite 20 is the result of filling the pores 16 of structure 10.However, the pores 16 of the structure 10 can be left open. Themicroporosity found in the structure 10 of composite 20 may, withoutbeing bound by the theory, function in that it allows for the absorptionof fluid throughout the composite 20 and the diffusion of degradationproducts out of the composite 20. This allows the composite 20 todegrade in an even manner from the inside out, results in a gradualtransition of load to the newly regenerating tissue. In instances whereacid based polymers such as PLA and PGA are used as the second material21 within the composite 20, the microporosity in the ceramic allows theacidic products to leave the implant and be absorbed by the surroundingtissue in a timely manner.

As discussed above, the second material 21 injected into the structure10 may fill the pores 16 of the structure 10 and yet maintain an openmicroporosity. The effect of this microporosity and/or continuous phaseaspects of the composite 20 on the degradation of a continuous phasecomposite 20 is shown in FIG. 3. The graph in FIG. 3 illustrates theresults of an experiment where degradation was conducted in a generallyknown phosphate buffer solution held at about body temperature (about37° C.) The degradation profile of a continuous phase composite 20composed of PLDLLA (the second material 21) and Pro Osteon 500R™(structure 10) was compared to a pure polymer sample composed of onlyPLDLLA. In FIG. 3, the graph of compressive strength over time shows agenerally even and linear degradation profile of the composite 20 (line30) when compared to a faster drop in strength seen with the purepolymer device (line 32). Although the same polymer was used in both thecomposite 20 and pure polymer specimens, the graph clearly shows theimpact of the composite 20.

As illustrated in FIG. 3, in various embodiments, the compressivestrength of the pure PLDLLA sample does not change over a significantlife span of the implant. Nevertheless, after about 150 days, a drop incompressive strength is illustrated. Therefore, during a majority of thelife span of the PLDLLA implant, the compressive strength does notchange, however, near the end of the life span of the PLDLLA implant,the compressive strength may degrade rapidly. A more even and lineardrop in compressive strength may be selected for various applications.This may allow for an even and gradual loading of an area of the anatomynear the implant of the composite 20.

Examining the composite 20 degradation profile, as illustrated by line32, the compressive strength of the composite 20 is substantially linearover its lifetime. The degradation of the compressive strength of thecomposite 20 does not include any long periods of maintenance of asingle strength, or a steep drop off at any particular time. Asubstantially linear decrease in compressive strength over time in thedegradative environment, such as an anatomical environment, allows forthe gradual loading of healing tissue with additional stresses.

For example, when an implant is used as a bone replacement, it may bedesirable to have a substantially continuous increase in stressesrelative to the implant. As is known to one skilled in the art, theincrease of stresses relative to the bone may increase or enhance boneingrowth into the area. Particularly, in a resorbable implant, it isdesirable to increase or enhance bone ingrowth into the area where theimplant has been degraded. As the implant degrades, the stresses aretransferred to the surrounding bone, and the new tissue slowly becomesload-bearing.

In various embodiments, the composite 20 exhibits a linear decrease incompressive strength as shown FIG. 3. In addition to the benefits of agradual transfer of forces to the new tissue, the composite 20 also canbe an excellent media for tissue ingrowth into the implant. This abilitywas demonstrated in a load-bearing bone defect model in the tibia andfemur of sheep. In such a model, typical solid polymer implants may showbone formation in limited amounts on the surface of the material. Withthe continuous phase composite 20, the resorption of the ceramicstructure 10 phase may allow eventual growth of bone into the center ofthe implant wall.

In various embodiments, the interaction of calcium carbonate and lacticacid from the polymer (the second material 21) phase results in aself-neutralizing reaction that eliminates some of the acid releasedfrom a degrading implant. This phenomenon further improves the long termbiocompatibility of the implant as seen by new bone formation in areasof active lactic acid degradation.

In various embodiments, in addition to the self-neutralizing ability ofthe composite 20, the presence of vascularized bone and residualmicroporosity also add to the overall biocompatibility of the degradingof the composite 20. Thus, tissue ingrowth in the pores 16 serves as ameans to transport degradation products from the site to thebloodstream. The blood vessels within an implant and the pores 16 systemallow degradation products to be cleared from the implant area in atimely manner.

In various embodiments, therapeutic agents are used in conjunction withthe composite 20. In general, therapeutic agents which may beadministered via the pharmaceutical compositions of the variousembodiments include, without limitation: anti-infectives such asantibiotics and antiviral agents; chemotherapeutic agents (i.e.anticancer agents); anti-rejection agents; analgesics and analgesiccombinations; anti-inflammatory agents; hormones such as steroids;growth factors, including bone morphogenic proteins (i.e. BMP's 1-7),bone morphogenic-like proteins (i.e. GFD-5, GFD-7 and GFD-8), epidermalgrowth factor (EGF), fibroblast growth factor (i.e. FGF 1-9), plateletderived growth factor (PDGF), insulin like growth factor (IGF-I andIGF-II), transforming growth factors (i.e. TGF-β I-III), vascularendothelial growth factor (VEGF); and other naturally derived orgenetically engineered proteins, polysaccharides, glycoproteins, orlipoproteins.

In various embodiments, the composite 20 may comprise at least one ofplatelet rich plasma (PRP), concentrated bone marrow aspirate andlipoaspirate cells. In various embodiments, the composite 20 may includehematopoietic stem cells, stromal stem cells, mesenchymal stem cells,endothelial progenitor cells, red blood cells, white blood cells,fibroblasts, reticulacytes, adipose cells, or endothelial cells. Any ofthe above cells, PRP, and/or concentrated bone marrow aspirate may beobtained by using centrifugation methods and an example of such methodsis disclosed in U.S. Patent Application Publication No. 2005/0109716. Invarious embodiments, composite may be soaked in at least one fractioncreated by centrifugation. The at least one fraction may include atleast one of PRP, concentrated bone marrow aspirate, lipoaspirate cells,hematopoietic stem cells, stromal stem cells, mesenchymal stem cells,endothelial progenitor cells, red blood cells, white blood cells,fibroblasts, reticulacytes, adipose cells, endothelial cells, any otherautologous tissue, and combinations thereof.

According to various embodiments, the composite 20 comprisesconcentrated bone marrow aspirate made by a method for concentratingbone marrow aspirate and blood including collecting bone marrow aspirateand blood from a patient then loading the bone marrow aspirate and bloodinto a separator that can separate the aspirate and the blood into threeor more fractions. The method includes centrifuging the separatorcontaining the bone marrow aspirate and the blood creating a fractionthat has a concentrated bone marrow aspirate and/or a concentratedblood. In various embodiments, such a concentration may be referred toas a buffy coat. The method also includes withdrawing the fractioncomprising the concentrate or buffy coat.

According to various embodiments, the composite 20 comprisesconcentrated bone marrow aspirate, blood, and/or a blood fraction. Suchmaterials may be derived by loading bone marrow aspirate and/or bloodinto a separator that can separate the bone marrow aspirate and/or bloodinto three or more fractions. The method also includes centrifuging theseparator then withdrawing a fraction comprising at least one of thegroup consisting of buffy coat, hematopoietic stem cells, stromal stemcells, mesenchymal stem cells, endothelial progenitor cells, red bloodcells, white blood cells, fibroblasts, reticulacytes, adipose cells, andendothelial cells, and then applying the fraction to an implantaccording to this technology, and implanting the implant.

Methods of Composite Manufacture

The composite 20 may also be formed by using any appropriate method,including such methods as are known to those skilled in the art.Generally, the second material 21 used to fill the selected porosity isadded to the structure 10 or otherwise used to fill the porosity of thestructure 10. In various embodiments, injection molding is used to forcemolten polymer (the second material 21) into the macroporosity of aporous ceramic structure 10. This can result in the composite 20including approximately 5-10% open microporosity. In variousembodiments, vacuum impregnation techniques may be used. Rather thanproducing a positive pressure on the melted polymer, a relatively lowpressure is formed in the structure 10 to pull the second material 21,which may be, for example, a bioresorbable polymer or a combinationthereof, into the porosity. Further techniques include solutionembedding where the second material 21 is dissolved and then cast intothe porosity.

In various embodiments, in situ polymerization techniques where thepolymer being used as second material 21 may be polymerized within theporosity of the structure 10 can be used to form the composite 20. Whenemploying in situ polymerization techniques, the structure 10 issubmerged in a reaction mixture of a monomer or a plurality of monomers,an initiator, and/or a catalyst and then heated to the reactiontemperature. The second material 21 (a polymer) is then formed in situwithin the porosity of the structure 10.

Other methods of forming the composite 20 are related to the use of aporous polymer matrix as the structure 10. The ceramic material is castwithin a porous, polymer matrix structure that forms the structure 10. Apolymer matrix may be formed to include a selected porosity and aceramic slurry may be positioned in the pores of the matrix. The ceramicslurry may then be forced to harden to form a solid or porous ceramicphase within the porosity of the structure 10. Thus, the composite 20may be formed by positioning the polymer in the structure 10 formed of aporous ceramic or by positioning a ceramic in the structure 10 formed ofa porous polymer.

Screw Implants

With reference to FIG. 4, an implant screw embodiment 70 is illustrated.In various embodiments, implant 70 may be an interference screw that canbe used to attach soft tissue to bone such as for ligament repair orreplacement, as described herein. The implant 70 demonstrates theversatility of the fabrication process by machining devices with both acomposite portion 74 which may be composite 20 and a polymer portion 76which may be the second material 21 or another bioresorbable polymer.For example, the implant 70 may include an external thread or engagementportion 72 composed of the composite portion 74 similar to the composite20. However, implant 70 can be machined from a composite 20 block withan excess polymer portion 76. This results in a dual region implant 70with a polymer portion 76 and a composite portion 74. Therefore, thecomposite portion 74 may be formed from a ceramic material (structure10), such as the Pro Osteon 500R™, that has been reinforced or injectedwith a polymer (the second material 21), such as the PLDLLA. Also, thepolymer portion 76 may be molded to the composite portion 74 accordingto various embodiments.

In addition, the polymer portion 76 may be composed of 100% PLDLLA. Sucha polymer portion 76 can improve the mechanical properties of theimplant 70 for various applications. For example, the polymer portion 76may provide a torsional strength that is greater than the torsionalstrength of the composite portion 74. Therefore, a tool engaging portion78 or area may be formed in the polymer portion 76 to allow for agreater torsional force to be applied to the implant 70 by a driver thatmay not be satisfied by the composite portion 74. The tool engagementportion 78 may include a hexagonal (hex or Allen), a slot, a square, atapered square (Robertson), an oval, a cruciform shape, a star (Torx®),a cross (Philips), or the like, that is an open shape through at least aportion of the center of the implant 70. A driver (not shown) isdesigned to engage with one of the above mentioned open shapes totransfer torque needed to screw implant 70 into a bone tunnel.

With regard to the fabrication of implant 70, this orientation ofpolymer portion 76 and composite portion 74 can be fabricated bydrilling holes within the porous structure 10 and then subjecting thestructure 10 to one of the composite fabrication techniques to introducethe second material 21 into the pores 16 of structure 10, as discussedabove. The addition of the second material 21 phase to the structure 10with pores 16, such as through injection molding, results in the fillingof the pores 16 in addition to creating the composite 20. Duringmachining, the implant 70 can be centered around a defined bore 80through the implant 70. The resulting implant 70 will have a polymerportion 76 on top of composite portion 74.

With reference to FIG. 5, an implant screw embodiment 90 is illustrated.In various embodiments, implant 90 may be an interference screw that canbe used to attach soft tissue to bone, such as for ligament repair orreplacement, as described herein. The implant 90 can also include tworegions, such as a composite region 92, which may be composite 20, and apolymer portion 94, which may be the second material 21 or anotherbioresorbable polymer. The composite region 92 may be substantiallysimilar to the composite 20 illustrated in FIG. 2. The addition of thepolymer portion 94 to the central area of the composite portion 92,however, can be used to achieve selected properties of the implant 90.For example, the polymer region 94 may provide a torsional strength thatis greater than the torsional strength of the composite portion 92.Therefore, a tool engaging portion 100 or area may be formed in thepolymer portion 94 to allow for a greater torsional force to be appliedto the implant 90 by a driver (not shown) that may not be satisfied bythe composite portion 92. The tool engagement portion 100 may include ahexagonal (hex or Allen), a slot, a square, a tapered square(Robertson), an oval, a cruciform shape, a star (Torx®), a cross(Philips), or the like, that is an open shape through at least a portionof the center of the implant 90. A driver (not shown) is designed toengage with one of the above mentioned open shapes to transfer torqueneeded to screw implant 90 into a bone tunnel.

With regard to the fabrication of implant 90, this orientation ofpolymer portion 94 and composite portion 92 can be fabricated bydrilling holes within the porous structure 10 and then subjecting thestructure 10 to one of the composite fabrication techniques to introducethe second material 21 into the pores 16 of structure 10, as discussedabove. The addition of the second material 21 phase to the structure 10with pores 16, such as through injection molding, results in the fillingof the pores 16 in addition to creating the composite 20. Duringmachining, the implant 90 can be centered around the central polymerportion 94 to define a bore 96 through the implant 90. The resultingimplant 90 will have a central polymer portion 94 surrounded by acomposite portion 92.

The implant 90 may be used for any appropriate purpose, and anengagement portion 98 may be formed on an exterior thereof. Theengagement portion 98 may be used to engage various structures, such asbone, such that the implant 90 may be an anchor or may define a screw.Further, a tool engagement portion 100 may be defined in the centralpolymer portion 94 for allowing engagement of a tool or driver (notshown) with the implant 90 for positioning the implant 90 in variousanatomical locations. The implant 90 may be used as a bone anchor, asuture anchor, a soft tissue anchor, a fracture screw, an interferencescrew, or any appropriate purpose.

With reference to FIG. 6, an implant screw embodiment 110 isillustrated. In various embodiments, implant 110 may be an interferencescrew that can be used to attach soft tissue to bone such as forligament repair or replacement, as described herein. The implant 110demonstrates the versatility of the fabrication process by machiningdevices with both a composite portion 112 which may be composite 20 anda polymer portion 114 which may be the second material 21 or anotherbioresorbable polymer. For example, the implant 110 may include anexternal thread or engagement portion 118 composed of a continuous phasecomposite that may be similar to the composite 20. However, implant 110can be machined from a composite 20 block with an excess polymer portion114. This results in a dual region implant with a polymer portion 114and a composite portion 112. Therefore, the composite portion 112 may beformed from a ceramic material (structure 10), such as the Pro Osteon500R™, that has been reinforced or injected with a polymer (the secondmaterial 21), such as the PLDLLA. Also, the polymer portion 114 may bemolded to the composite portion 112, according to various embodiments.

In addition, the polymer portion 114 may be composed of 100% PLDLLA.Such a polymer portion 114 can improve the mechanical properties of theimplant 110 for various applications. For example, the polymer portion114 may provide a torsional strength that is greater than the torsionalstrength of the composite portion 112. Therefore, a tool engagementportion 116 or area may be formed in the polymer portion 114 to allowfor a greater torsional force to be applied to the implant 110 by adriver that may not be satisfied by the composite portion 112. The toolengagement portion 116 may include a hexagonal (hex or Allen), a slot, asquare, a tapered square (Robertson), an oval, a cruciform shape, a star(Torx®), a cross (Philips), or the like, that is an open shape throughat least a portion of the center of the implant 110. A driver (notshown) is designed to engage with one of the above mentioned open shapesto transfer torque needed to screw implant 110 into a bone tunnel.

With regard to the fabrication of implant 110, this orientation ofpolymer portion 114 and composite portion 112 can be fabricated bydrilling holes within the porous structure 10 and then subjecting thestructure 10 to one of the composite fabrication techniques to introducethe second material 21 into the pores 16 of structure 10, as discussedabove. The addition of the second material 21 phase to the structure 10with pores 16, such as through injection molding, results in the fillingof the pores 16 in addition to creating the composite 20. Duringmachining, the implant 110 can be centered around the central toolengagement portion 116 to define a bore 80 through the implant 110. Theresulting implant 110 will have a central polymer portion 114 surroundedby a composite portion 112.

With reference to FIG. 7, an implant screw embodiment 130 isillustrated. In various embodiments, implant 130 may be an interferencescrew that can be used to attach soft tissue to bone, such as forligament repair or replacement as described herein. The implant 130 canbe made as a composite portion 132, which may be composite 20. Thecomposite portion 132 may be substantially similar to the composite 20illustrated in FIG. 2. Therefore, a tool engaging portion 140 or areamay be formed in the composite portion 132 to allow for a torsionalforce to be applied to the implant 130 by a driver. The tool engagementportion 140 may include a hexagonal (hex or Allen), a slot, a square, atapered square (Robertson), an oval, a cruciform shape, a star (Torx®),a cross (Philips), or the like, that is an open shape through at least aportion of the center of the implant 130. A driver (not shown) isdesigned to engage with one of the above mentioned open shapes totransfer torque needed to screw implant 130 into a bone tunnel.

Implant 130 can be fabricated by drilling holes within the porousstructure 10 and then subjecting the structure 10 to one of thecomposite fabrication techniques to introduce the second material 21into the pores 16 of structure 10, as discussed above. The addition ofthe second material 21 phase to the structure 10 with pores 16, such asthrough injection molding, results in the filling of the pores 16 inaddition to creating the composite 20. During machining, the implant 130can be centered around the central tool engagement portion 140 to definea bore 136 through the implant 130. The resulting implant 130 will havea tool engagement portion 140 surrounded by a composite portion 132.

The implant 130 may be used for any appropriate purpose, and anengagement portion 138 may be formed on an exterior thereof. Theengagement portion 138 may be used to engage various structures, such asbone, such that the implant 130 may be an anchor or may define a screw.Further, a tool engagement portion 140 may be defined in the compositeportion 132 for allowing engagement of a tool with the implant 130 forpositioning the implant 130 in various anatomical locations. The implant130 may be used as a bone anchor, a suture anchor, a soft tissue anchor,a fracture screw, an interference screw, or any appropriate purpose.

In various embodiments, interference screws, such as implant 70, 90,110, 130 may be sized so that they are slightly larger that the diameterof the tunnel, so that they dilate the bone tunnel upon insertion.Dilation advantageously compacts the soft cancellous bone between theends of the tunnel, providing better fixation. Conventionalstraight-sided bioabsorbable interference screws have an interferencefit of about 1 mm such that about 1 mm of bone is dilated as the screwis inserted into the bone tunnel.

Implants, such as the implants 70, 90, 110, 130, according to variousembodiments, may be formed in many different ways and include differentstructures. Those described above are merely exemplary in nature and notintended to limit the present teachings herein. For example, an implant70, 90, 110, 130 may include an exterior thin coat formed around apolymer interior, or vice-versa. The exterior thin coat may include athickness that is substantially less than that of the interior portion,but provide selected properties to an implant.

With reference to FIG. 8, an implant screw embodiment 170 isillustrated. The implant 170 may define a screw or anchor portion thatmay be positioned relative to a selected portion of the anatomy. Theimplant 170 may define a thread 172 that extends along a length of theimplant 170 from a first or insertion end 174 to a second or driving end176. The thread 172 may or may not extend the entire length of theimplant 170.

Regardless, the implant 170 may define the thread 172 and the drivingend 176 such that the implant 170 may be inserted into a selectedportion of the anatomy. Similar to the implants 70, 90, 110, 130illustrated in FIGS. 4-7 above, the implant 170 may be used to fix aselected soft tissue therein, fix a structure thereto, or otherappropriate procedures. For example, in a generally known anteriorcruciate ligament replacement, the implant 170 may define aninterference screw to assist in holding the graft in a selectedposition.

The implant 170 may be formed substantially completely of the composite20. It will be understood that the implant 170 or the implants describedabove, according to various embodiments, may be provided for variousprocedures or purposes. As is generally understood in the art, a graftmay be positioned or provided of soft tissue to interconnect a femur anda tibia. The implant 170 may be used to substantially hold the softtissue portion relative to a selected portion of the anatomy. Asdiscussed above, the composite material forming the implant 170 may beabsorbed into the anatomy at a selected rate to allow for bone ingrowthand fixation, such as generally anatomical fixation, of the soft tissuemay be provided. In various embodiments, implant 170 may comprise acomposite region and a polymer region, as well as tool engagement, asillustrated and described above in FIGS. 4-7.

An implant screw embodiment 200 in FIG. 9 can be used for fracturerepair. In various embodiments, implant 200 may be used as aninterference screw in ligament repair or replacement, as describedherein. The implant 200 may include an extended shaft that defines athread 202 along all or a portion of the shaft. A driving end 204 mayalso be provided to assist in driving the implant 200 into the selectedimplant site. The thread 202 defined by the implant 200 may be driveninto a pre-formed bore, a tapped bore, an untapped bore, or anypredefined void. Further, the implant 200 may be formed in appropriatedimensions, such as a length, thickness, thread height, etc., to achieveselected results. The implant 200 may also be cannulated and have asimilar composition and tool engagement to the dual region implant 70,90, 110 and 130 as illustrated and described above in FIGS. 4-7.

With reference to FIG. 10, an implant screw embodiment 220 isillustrated. The implant 220 may include a suture anchor or define asuture anchor to assist in holding a selected suture 222 used in softtissue repair. For example, the suture 222 may be to reattach a softtissue region to bone or other soft tissue. In various embodiments,implant 220 may be used as an interference screw in ligament repair orreplacements as described herein. The implant 220 may define a shaft orbody including a first end 224 and a second end 226. The body of theimplant 220 may further have a first engaging or interference portion228 extending therefore. Further, a second interference portion 230 mayalso be provided.

The implant 220 may then be driven into the bone of the soft tissuefixation site. The suture 222 is then used to affix the soft tissue tobone. The implant 220 may be generally driven into a bore formed in theportion of the anatomy including a diameter less than a diameter ordimension of the interference portions 228, 230. Therefore, the implant220 may form an interference fit with a selected portion of the anatomyto hold the suture 222 relative to the selected portion of the anatomy.The implant 220 may also be cannulated and have a similar compositionand tool engagement to the dual region implant 70, 90, 110 and 130 asillustrated and described above in FIGS. 4-7.

Method of Manufacturing Implants

With reference to FIG. 11, an implant 350 may be formed according to theillustrated method 351. A blank 356 may be formed of the structure 10.The structure 10 may be any appropriate porous material, such as apolymer matrix, ceramic, or the like. The blank 356 may also be shapedinto any appropriate geometry, such as a cylinder.

The blank 356 may then be injected with the second material 21, such asa polymer, as discussed above. This may create polymer portions 358 thatextend from a composite 352 that may be similar to the composite 20. Theinjection may occur by melting the second material 21 and injecting itunder pressure into the pores 16 and/or channels defined by the blank356. The composite 352 may then have the exterior polymer portions 358removed to include substantially only the composite 352.

A fill material 354 such as, for example, polymer, may then be insertedinto the composite 352 form. The fill material 354 may be anyappropriate material. For example, the fill material 354 may besubstantially similar to the material that formed the blank 356. The twoportions, including the fill material 354 and the composite 352, maythen be heated to meld the two together to form the implant 350. In theimplant 350, the fill material 354 may be formed into the implant 350and provided complete for a procedure. Thus, implant 350 may be formedto include voids or pre-filled voids. The fill material 354 may servethe same purpose as the graft material discussed above, such as a voidfilling or support purposes. Nevertheless, the implant 350 may includethe fill material 354 and be manufactured with the fill material 354.

With reference to FIG. 11, a flow chart describes a method 400 forforming an implant according to various embodiments. The method 400 maybegin at a start block 401. Then a selected implant region is selectedin block 402. The implant region may be any appropriate region of theanatomy. For example, a spinal region, a tibial region, a femoralregion, a humeral region, or the like may be selected. As discussedabove, an implant may be formed for any appropriate portion of theanatomy using the composite 20.

After the implant region is selected in block 402, loads may bedetermined relative to that the region in block 404. For example, acompressive force, shear force, torsion force, or the like, may bedetermined at the selected region of the anatomy. For example, it may bedetermined that about 1500 N to about 3000 N may be experienced in aspinal region. Although other forces may be determined, the forces maydepend upon a patient, the region selected, and other considerations.

Also, other forces that the implant may experience can be determined.For example, a torsion stress necessary for implantation may bedetermined. Thus, not only forces in the selected region of the anatomy,as selected in block 402, but other forces may be determined in block404. Properties of an implant may then be determined in block 406. Forexample, after the experienced forces are determined in block 404, theforces that the implant may be required to withstand, for variousreasons, can be determined. Therefore, the loads determined in theanatomical region may be different than those determined as a propertyof the implant in block 406, but they may be related.

Also, a selected resorption time may be a property selected in block406. For example, a resorption time of the implant may depend uponselected loads in the region of the anatomy or ingrowth rates at theselected regions, or other selected reasons. Thus, the resorption timeor profile of the implant may be determined in block 406. In thisregard, bond ingrowth in various regions of the body may vary dependingon the region, loads encountered and anatomical condition of the area ofinterest.

Then implant materials may be determined in block 408. The materialsselected may be the appropriate material to form the structure 10 or theappropriate second material 21 for the fill of the pores 16. Although,as discussed above, both the structure 10 and the fill for the pores 16can be polymers or both can be ceramic materials. Also, the implantmaterials may be selected to achieve the selected properties, such as astrength, strength degradation profile, resorption profile,load-bearing, etc. As also discussed above, the materials selected maybe a second material 21 of a selected molecular weight, a certainco-polymer, etc.

Also, the configuration or form of the implant can be determined whendetermining the implant materials in block 408, or at any appropriatetime. As discussed above, the implant may include a composite portion(such as composite 20) and a noncomposite portion (such as secondmaterial 21). Therefore, to achieve the determined properties of theimplant, such designs may also be determined in block 408.

Then the implant can be formed in block 410. The implant may be formedof the materials determined in block 408 and the configurationdetermined in block 408. The implant may be formed according to anyappropriate method and the formation method may also be chosen dependingupon a selected property. For example, the second material 21 may bemelted and then injected into the porous structure 10. Nevertheless, anyappropriate method may be used to form the implant in block 410.

The implant formed in block 410 may then be implanted in block 412. Asdiscussed above, the implant may be customized by a user prior toimplantation or it may be implanted as formed in block 410. Also, agraft material may be used with the implant formed in block 410, also asdiscussed above. Generally, however, after the implant is formed inblock 410, it can be implanted in block 412. Then, generally, the method400 ends in block 414.

The method 400, however, is merely exemplary and an implant may beformed of the composite 20 according to any appropriate method. Theimplant formed according to method 400 can include a selected propertyto achieve selected results after implantation. The selected propertiescan be achieved by selecting appropriate materials for the compositeimplant, a selected configuration of the implant, or other appropriateconsiderations.

Also, regardless of the method chosen, the composite 20 may be used toform an implant that includes a selected strength over a selected periodof time, yet can still allow ingrowth of bone. The composite 20 may beformed into an implant where bone may grow into regions that are fasterresorbing than other regions. This may be created by including thefaster resorbing phase and the slower resorbing phase. The difference inresorption rates may be any appropriate difference, such as about 10%different to about 200% different. Regardless, the slower resorbingphase may be selected for a strength quality to achieve a selectedstrength degradation profile, while the faster responding phase may beselected based upon the bone regrowth rate of the area of interest. Thiscan assist in bone regrowth and in allowing recovery when a resorptionmay be selected in a load-bearing area of the anatomy. This may also beused to achieve a selected strength of the implant for a selected periodfor any appropriate purpose.

As otherwise understood, the method 400 can be used to select materialsand properties of the materials for a selected or unique application.The known or determined bone growth rate of a selected region of theanatomy can be used to assist in determining the materials to be used informing the implant, the ratios of the materials to be used, or thespecific properties of the materials to be used. Also, the forces thatare experienced in a selected region of the anatomy may be used toselect the materials to be used to form an implant. Thus, a higherselected strength may be used to select different materials for formingthe implant. Therefore, the method 400 may be used to select materialsfor an implant, select a structure of an implant, or selected otherfeatures of the implant.

Methods of Treatment

The present technology provides methods of using the implants orimplantable screws disclosed herein for tissue repair, includingligament repair procedures. The ACL and PCL procedures, for example, maybe performed arthroscopically and, generally, involve preparing a bonetunnel through the tibia and adjacent femur, placing a ligament graftextending between the two bone tunnels, and securing each end of thegraft within its respective tunnel.

One common method of ACL reconstruction employs the use ofbone-tendon-bone ligament grafts bone ligament grafts (harvested fromthe patella and tibia) where the bone block at each end of the graft isfixed within its respective tunnel by an implantable interference screwsecured within each tunnel between the tunnel wall and the adjacent boneblock. The interference screw is aligned parallel to the axis of thetunnel and holds the bone block in the tunnel by wedging it against thetunnel wall opposite the interference screw and by engaging the boneblock and the adjacent tunnel wall with the interference screw threads.Another common method employs the use of soft tissue grafts(semitendinosus, hamstring, Achilles, quadriceps, etc.) where the endsof the graft are secured by an interference screw similarly interposedbetween the wall of the bone tunnel and the adjacent soft tissue of thegraft.

A widely used technique for the reconstruction of the ACL is known asthe Jones procedure. The basic steps in the procedure include harvestinga graft made from a portion of the patellar tendon with attached boneblocks; preparing the graft attachment site by drilling holes inopposing bones of the joint in which the graft will be placed; placingthe graft in the graft attachment site; and rigidly fixing the boneblocks in place within the graft site, in the holes or bone tunnels. Theinterference screws used to fix the graft in place are wedged betweenthe bone block and the wall of the hole into which the bone block fits.Typically, there is very little space between the bone block and thehole in the bone at the fixation site. See, for example, U.S. Pat. Nos.4,870,957; 4,927,421; 4,950,270; 5,062,843; 5,300,077; 5,931,869;6,019,797; 6,254,604; 6,264,694; 6,280,472; 6,280,840; 6,354,604;6,482,232; 6,755,840; 6,905,513; 6,916,321; and 7,033,364.

With reference to FIGS. 13 and 14, a general method for ACLreconstruction is outlined. Substitute ligament 206 may be anaudiograph, such as a patellar tendon, a portion of a patellar tendonharvested from a patient, or may be a ligament or a tendon harvestedfrom another part of the patient's body such as from a hamstring, anAchilles tendon, or the fascia lata. In various embodiments, thesubstitute ligament 206 may be synthetic. A hole or a first tunnel 203is drilled in the femur 208. A second tunnel 218 is drilled in the tibia208. The substitute ligament 206 may be bundled and sutures 212, 213 areadded at either end using a guide wire in suture 204, the substituteligament 206 is pulled through the second tunnel 218 and the through thefirst tunnel 203. Tunnels 203,218 may be bore using a drill bit and mayemploy additional tools such as a tubular tunnel guide and a dilationtool, to create a proper hole in a proper position. Tunnels 203, 218 maybe started using a pilot tool. Once the substitute ligament 206 has beenpulled through the tunnels 203, 218 a first interference screw 201 isdriven into first tunnel 203 such that threads of the first interferencescrew 201 engage in the walls of the first tunnel 203 and substituteligament 206. The first interference screw 201 is driven using driver219. After the fixation of the first interference screw 201, such thatligament 206 is secure, tension tool 215 pulls suture 212 with a knownforce 214. Such known force 214 may be between about 50 N and about 100N. As force 214 is applied to substitute ligament 206, the secondinterference screw 209 is driven into the second tunnel 218. The secondinterference screw 209 may be driven into femur 208 using a guide 207 toensure that it has been driven into femur 208 correctly. The secondinterference screw 209 engages the wall of second tunnel 218 and thesubstitute ligament 206 such that the substitute ligament 206 is affixedand secure within femur 208. In some embodiments, substitute ligament206 may include bone block at either end of the substitute ligament 206such that the interference screws (201, 209) engage the bone block andthe wall of the tunnel. In various embodiments, interference screws 201,209 may be any of the interference screws 70, 90, 110, 130, 170, 200,220 and their equivalents, as described above. In various embodiments,interference screws 201, 209 may be comprise autologous tissue which mayinclude at least one of platelet rich plasma, concentrated bone marrow,and lipoaspirate cells.

In various embodiments, therapeutic agents are used in conjunction withthe interference screws 201, 209. In general, therapeutic agents whichmay be administered in various embodiments include, without limitation,anti-infectives such as antibiotics and antiviral agents;chemotherapeutic agents (i.e. anticancer agents); anti-rejection agents;analgesics and analgesic combinations; anti-inflammatory agents;hormones such as steroids; growth factors, including bone morphogenicproteins (i.e. BMP's 1-7), bone morphogenic-like proteins (i.e. GFD-5,GFD-7 and GFD-8), epidermal growth factor (EGF), fibroblast growthfactor (i.e. FGF 1-9), platelet derived growth factor (PDGF), insulinlike growth factor (IGF-I and IGF-II), transforming growth factors (i.e.TGF-β I-III), vascular endothelial growth factor (VEGF); and othernaturally derived or genetically engineered proteins, polysaccharides,glycoproteins, or lipoproteins.

In various embodiments, interference screws 201, 209may comprise atleast one of platelet rich plasma (PRP), concentrated bone marrowaspirate, and lipoaspirate cells. In various embodiments, interferencescrews 201, 209 may comprise at least one of hematopoietic stem cells,stromal stem cells, mesenchymal stem cells, endothelial progenitorcells, red blood cells, white blood cells, fibroblasts, reticulacytes,adipose cells, or endothelial cells. Any of the above cells, PRP, and/orconcentrated bone marrow aspirate may be obtained by usingcentrifugation methods and an example of such methods is disclosed inU.S. Patent Application Publication No. 2005/0109716. In variousembodiments, composite may be soaked in at least one fraction created bycentrifugation. The at least one fraction may include at least one ofPRP, concentrated bone marrow aspirate, lipoaspirate cells,hematopoietic stem cells, stromal stem cells, mesenchymal stem cells,endothelial progenitor cells, red blood cells, white blood cells,fibroblasts, reticulacytes, adipose cells, endothelial cells, any otherautologous tissue and combinations thereof.

According to various embodiments, interference screw 201, 209 compriseconcentrated bone marrow aspirate made by a method for concentratingbone marrow aspirate and blood, including collecting bone marrowaspirate and blood from a patient, then loading the bone marrow aspirateand/or blood into a separator that can separate the bone marrow aspirateand/or blood into three or more fractions. The method includescentrifuging the separator containing the bone marrow aspirate and theblood creating a fraction that has a concentrated bone marrow aspirateand/or a concentrated blood component. In various embodiments, such aconcentration may be a buffy coat. The method also includes withdrawingthe fraction comprising the concentrate or buffy coat.

According to various embodiments, interference screw 201, 209 comprisesconcentrated bone marrow aspirate and/or blood, or a blood fraction.Such materials may be derived by loading bone marrow aspirate and/orblood into a separator that can separate the bone marrow aspirate and/orblood into three or more fractions. The method also includescentrifuging the separator then withdrawing a fraction comprising atleast one of the group consisting of buffy coat, hematopoietic stemcells, stromal stem cells, mesenchymal stem cells, endothelialprogenitor cells, red blood cells, white blood cells, fibroblasts,reticulacytes, adipose cells, and endothelial cells, then applying thefraction to an implant according to disclosure, and implanting theimplant.

In various embodiments, a kit may include at least one interferencescrew such as those interferences screws described herein and, morespecifically, interference screws 70, 90, 110, 130, 170, 200, 220; and adriver operable to drive the screw into a tunnel in a patient's bone. Invarious embodiments, the kit of the interference screw comprises a toolengagement area that cooperates with the driver. The total engagementarea may have a cross-sectional area of a hexagonal (hex or Allen), aslot, a square, a tapered square (Robertson), an oval, a cruciformshape, a star (Torx®), or a cross (Philips). In various embodiments, thekit further comprises at least one of a drill bit, a dilator, a tibiatunnel guide, a modular guide, a graft prep table, bone coringinstrument, a tibial reamer, an imprigment rod, a femoral aimer, anacorn reamer, a washer, a top, a guide wire, a dilator, a pull-throughsuture, and a pilot hole tool.

The various embodiments and the examples described herein are exemplaryand not intended to be limiting in describing the full scope ofcompositions and methods of this technology. Equivalent changes,modifications, and variations of the various embodiments, materials,compositions, and methods can be made within the scope of the presenttechnology with substantially similar results.

What is claimed is:
 1. An implantable interference screw for use in softtissue repair, the screw comprising: a substantially-cylindrical ceramicbody having a tapered end, at least a portion of said ceramic bodycomprising a plurality of interconnected pores; an instrument interfaceat the end of said ceramic body opposite to said tapered end, wherein afirst volume of a bioresorbable polymer is structurally reinforcing saidinstrument interface; a thread starting near said tapered end, andsurrounding at least a portion of a surface of said ceramic body; and asecond volume of the bioresorbable polymer filling at least a portion ofsaid plurality of interconnected pores.
 2. A screw according to claim 1further comprising a coating covering at least a portion of a surface ofsaid plurality of interconnected pores.
 3. A screw according to claim 1wherein said plurality of pores have a size of from about 350 microns toabout 550 microns.
 4. A screw according to claim 1 wherein said ceramicbody is bioresorbable.
 5. A screw according to claim 4 wherein saidceramic body and said bioresorbable polymer are bioresorbable atdifferent rates.
 6. A screw according to claim 1 wherein said ceramicbody comprises a material selected from the group consisting of calciumphosphate, calcium carbonate, calcium oxide, calcium sulfate,hydroxyapatite, magnesium calcium phosphate, and combinations thereof.7. A screw according to claim 1 wherein said bioresorbable polymer isselected from the group consisting of aliphatic polyesters,polyorthoesters, polyanhydrides, polycarbonates, polyurethanes,polyamides and polyalkylene oxide, and combinations thereof.
 8. A screwaccording to claim 1 wherein said instrument interface comprises an openarea in said interface having a cross-sectional shape selected from thegroup consisting of a hex, an oval, a slotted square, a tapered square,a cruciform, a cross, and a star.
 9. A screw according to claim 1further comprising at least one of platelet rich plasma, concentratedbone marrow aspirate and lipoaspirate cells.
 10. A screw according toclaim 9 wherein said at least one of the platelet rich plasma,concentrated bone marrow aspirate, and lipoaspirate cells are isolatedby centrifugation.
 11. A kit for surgical repair of an ACL, the kitcomprising: a drive tool; and at least one interference screwcomprising, a bioabsorbable ceramic structure having a plurality ofinterconnected pores filled with a bioabsorbable polymer, saidinterference screw having an elongated threaded body, the elongatedthreaded body having a proximal end, a distal end, a length, a thread,and a taper, the thread of the interference screw extendingsubstantially along the entire length of the interference screw fromsaid proximal end to said distal end, the elongated threaded body havinga hollowed area in the proximal end operable for engagement of saiddrive tool, said hollowed area reinforced with said bioabsorbablepolymer.
 12. A kit according to claim 11 further comprising at least oneof a drill bit, a dilator, a tibia tunnel guide, a modular guide, agraft prep table, a bone coring instrument, a tibial reamer, animprigment rod, a femoral aimer, an acorn reamer, a top, a washer, aguide wire, a dilator, a pull-through suture, and a pilot hole tool. 13.An interference screw comprising a substantially cylindrical ceramicbody having a tapered end and a thread starting near said tapered end,the body further comprising: a bioabsorbable ceramic scaffold having aplurality of interconnecting channels; a first volume of a bioabsorbablepolymer in a majority of said plurality of interconnecting channels; anda tool engagement region that is reinforced with a second volume of saidbioabsorbable polymer.
 14. A screw according to claim 13 furthercomprising an autologous tissue filling a minority of said plurality ofinterconnecting channels including at least one of platelet rich plasma,concentrated bone marrow aspirate, and lipoaspirate cells.
 15. A screwaccording to claim 13 wherein the tool engagement region is in a hollowarea of said body and threads surround the exterior of the body from thetapered end to a substantially flat top, said top having a hole incommunication with the hollow area.
 16. A screw according to claim 13wherein said tool engagement region has a cross-sectional area that hasa shape selected from the group consisting of a hex, an oval, a slottedsquare, a tapered square, a cruciform, a cross, and a star.
 17. A screwaccording to claim 13 wherein said interconnecting channels have a sizeof from about 350 microns to about 550 microns.
 18. A screw according toclaim 13 wherein said bioabsorbable ceramic scaffold and saidbioabsorbable polymer are bioresorbable at different rates.
 19. A screwaccording to claim 13 wherein said bioabsorbable ceramic scaffold andsaid bioabsorbable polymer are bioresorbable at the same rates.
 20. Ascrew according to claim 13 wherein said bioabsorbable ceramic scaffoldcomprises a material selected from the group consisting of calciumphosphate, calcium carbonate, calcium oxide, calcium sulfate,hydroxyapatite, magnesium calcium phosphate, and combinations thereof.21. A screw according to claim 13 wherein said bioabsorbable polymer isselected from the group consisting of aliphatic polyesters,polyorthoesters, polyanhydrides, polycarbonates, polyurethanes,polyamides and polyalkylene oxide, and combinations thereof.
 22. A screwaccording to claim 13 further comprising at least one of platelet richplasma, concentrated bone marrow aspirate, and lipoaspirate cells.
 23. Ascrew according to claim 22 wherein said at least one of the plateletrich plasma, concentrated bone marrow aspirate, and lipoaspirate cellsis isolated by centrifugation.
 24. An implantable interference screwsystem for use in soft tissue repair, the screw comprising: asubstantially-cylindrical ceramic body having a tapered end, at least aportion of said body comprising a plurality of interconnected pores; aninstrument interface at the end of said body opposite to said taperedend with a first bioresorbable polymer structurally reinforcing saidinstrument interface and contained within a perimeter of said body; athread starting near said tapered end, and surrounding at least aportion of a surface of said body; and a second bioresorbable polymer,other than the first bioresorbable polymer, filling at least a portionof said plurality of interconnected pores.
 25. A system according toclaim 24, wherein said instrument interface includes a hollowed regionin an end of said body operable for engagement of an instrument.
 26. Asystem according to claim 25, further comprising: said instrument,wherein said instrument engages the reinforced hollowed region through ahole in the end of the body to transfer a torque from the saidinstrument to said thread.
 27. A system according to claim 24, whereinsaid plurality of pores includes a first sub-plurality of the pluralityof pores having a first size range from about 100 microns or less and asecond sub-plurality of the plurality of pores having a second sizerange from about 100 μm or greater; wherein the second bioresorbablepolymer fills substantially only the second sub-plurality of theplurality of pores.
 28. A system according to claim 24, whereininterstitial spaces are between the plurality of interconnected poreswithin said body.
 29. A system according to claim 25 further comprising:an autologous tissue filling a minority of said plurality ofinterconnecting pores; wherein said autologous tissue is selected from agroup consisting of platelet rich plasma, concentrated bone marrowaspirate, and lipoaspirate cells.